The aim of this present case series investigated the effect of a combination therapy utilizing connective tissue graft (CTG) in the treatment of periodontal regeneration of mandibular Class Ⅲ furcation involvement (FI). Six patients diagnosed with periodontitis stage Ⅲ or Ⅳ (grade A to C), presenting with Class Ⅲ or Ⅳ FI, were treated with fibroblast growth factor 2 and carbonate apatite in combination with CTG. The following clinical parameters were evaluated at baseline and after 6, 12 and 18 months: periodontal probing depth, clinical attachment level, furcation invasion, the radiographic vertical defect depth, and gingival phenotype. Significant improvements in clinical parameters were observed in all treated FI sites. Four Class Ⅲ Fls and one Class Ⅳ Fl obtained complete closure, and one Class Ⅳ furcation was improved to Class Ⅰ. This case series showed the potential of administering combination regenerative therapy for changing the prognosis of hopeless teeth with severe furcation defects.